Anticancerous Potential of Plant y Fitoquimicos

8/11/2019 Anticancerous Potential of Plant y Fitoquimicos

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Anticancerous Potential of

Plant Extracts andPhytochemicals

By

Arti Goel

ISSN 0970-4973 (Print)ISSN 2319-3077 (Online/Electronic)

J. Biol. Chem. ResearchVolume 30 (2) 2013 Pages No. 537-558

Journal ofBiological andChemical Research(An International Journal of Life Sciences and Chemistry)

Published by Society for Advancement of Sciences


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J. Biol. Chem. Research. Vol. 30, No. 2: 537-558 (2013)(An International Journal of Life Sciences and Chemistry)

Ms 30/2/78/2013, All rights reserved

ISSN 0970-4973 (Print)ISSN 2319-3077 (Online/Electronic)Published by Society for Advancement of Science

http:// www.jbcr.in

[email protected]

[email protected]

REVIEW ARTICLE

Received: 14/06/2013 Revised: 18/07/2013 Accepted: 20/07/2013

Anticancerous Potential of Plant Extracts and

Phytochemicals

Arti GoelAmity Institute of Microbial Biotechnology, Amity University, Sector- 125,

Noida, 201301, (U.P.), India

ABSTRACT

There is a demand for nat ural source of pest icides in food, cosmet ics & therapeut ic

industr y. Due to their low cost , high stability, compat ibilit y and environment f riendly,

we found that plants are the good source of natural antim icrobial agents due to the

presence of phytochemicals. Plant extracts appears to be one of the bet ter alternat ives

as they are known to have minimal environmental impact and danger t o consumers incontrast to synthetic pesticides. The use of and search for drugs and dietary

supplements derived from plants have accelerated in recent years. Ethno-

pharmacologists, botanists, microbiologists, and natural products chemists are

combining the Eart h for phytochemicals and " leads" which could be developed for

treatment of infectious diseases. Many pathogenic microbes have capability to

develop resistance against synthetic formulat ion. Synthetic formulat ion is very toxic

and destroys the soil fer t ilit y and ecological balance. Plant based formulat ion are least

toxic and better for environment balance so it can be replace by synthetic formulat ion.

Antimicrobial activity of plants is mainly due to the presence of secondary

metabolit es. Plant s are rich in w ide variety of secondary metaboli tes such as tannins,terpenoids, alkaloids, and flavonoids, which have been found in vitro to have

antim icrobial properties. This review att empts to summarize the current status of

phytochemicals to prot ect one against cancer.

Keywords: Phytochemicals, Anticancerous potential, Plant Extracts, Secondary

Metabol it es and Infect ious diseases.


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Ant icance rous ..Ph yt oche mi ca ls Goel , 20 13

INTRODUCTIONMedicinal plants have been used as remedies for human diseases for centuries. Thereason for using them as medicine lies in the fact that they contain chemical

components of therapeutic value (Nostro et al. 2000). The medicinal value of plants liesin some chemical substances (usually secondary metabolites), that produce a definitephysiological action on the human body. The most important of these bioactivecompounds of plants are alkaloids, flavanoids, tannins and phenolics (Edeoga et al.2005).

Phytochemicals are non-nutritive plant chemicals that work with nutrients and dietaryfiber to protect one against diseases. There are more than a thousand knownphytochemicals. They are not essential nutrients and are not required by the humanbody for sustaining life. Research suggests that phytochemicals, found in fruits,

vegetables and nuts, may help slow the aging process and reduce the risk of manydiseases, including cancer, heart disease, stroke, high blood pressure, cataracts,osteoporosis, and urinary tract infections. Foods containing phytochemicals are alreadypart of our daily diet. In fact, most foods contain these chemicals except for somerefined foods such as sugar or alcohol. Some foods, such as whole grains, vegetables,beans, fruits, and herbs, contain many phytochemicals. The easiest way to get morephytochemicals is to eat more fruit and vegetables. These biologically activemicronutrients exhibit their activity as antioxidants, detoxifying agents or simply byphysic-chemical means in the case of dietary fiber. They can have complementary andoverlapping mechanisms of action in the body, including antioxidant effects, modulationof detoxification enzymes, stimulation of the immune system, modulation of hormone

metabolism, and antibacterial and antiviral effect.

A RAINBOW OF PROTECTION

Cancer is the cause of more than six million deaths each year in the world. In 2001,about 1,268,000 new cancer cases and 553,400 deaths were reported in the UnitedStates. For a long time, plants are being used in the treatment of cancer. According toan estimate, 50% of breast cancer and 37% of prostate cancer patients use herbalproducts. Pigmented plant compounds are important anti-inflammatory and antioxidantsubstances, and people who eat more of them have a decreased risk of cancer. Plantpigments are mostly polyphenolic, meaning they are multiphenol-containing molecules,

and include chlorophyll, carotenoids and bioflavonoids. Green plants containparticularly large amounts of chlorophyll, which are a detoxifier and possibly ananticancer agent. Foods rich in chlorophyll include chlorellaand other blue-green algae,beet greens, bok choy, collards, dandelion greens, kale, mustard greens and nettles.These greens--among the most nutritious of all plants or plant parts--also contain otherdiverse nutrients and healthy constituents.

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The blue-green algae family has high chlorophyll content and has been credited withimmune-enhancing effects including stimulation of phagocytosis and enhancedresponse to tumors and microbes. Chlorella powder, specifically, may reduce side

effects of chemotherapy for some patients and may possess direct anticancer activities.Orange, yellow and red-orange foods are rich in carotenoids such as beta-carotene,lutein and lycopene. These constituents are antioxidants and anticancer agents due toseveral different mechanisms. More than 600 carotenoids occur naturally, but carotenesare the most widely known. Carotenes seem to offer protection against lung, colorectal,breast, uterine and prostate cancers. Carotenes, which destroy oxygen free radicals inlipids, enhance immune response and protect cells against UV radiation. Foods rich inthese flavonoids include apricots, carrots, citrus fruits, squash and tomatoes in additionto many green foods. The anthocyanidins are a type of complex flavonoid that producesblue, purple or red colors. Foods rich in these phytochemicals include beets,blackberries, blueberries, cherries, purple and red grapes, and purple cabbage.Anthocyanidins support connective tissue regeneration and are anti-inflammatory; theypromote blood flow and reduce cholesterol, in addition to being antioxidants.Anthocyanidins seem to stabilize and protect capillaries from oxidative damage andhave been shown to stabilize connective tissue, promote collagen formation, improvemicrocirculation and help protect blood vessels from oxidative damage. Thus, by eatingthese antioxidant pigments, some believe cancer risk can be reduced because theantioxidants protect against damage and help repair connective and vascular tissues.Proanthocyanidins are the precursors to anthocyanidins, and are comprised of smallerunits including catechins and epicatechins. Catechins are simple flavonoids that areabundant in green tea. Several Japanese studies show that tea consumption is

protective against breast and other types of cancer.PHYTOCHEMICAL DEFENCE

Detoxifying, stimulating and spicy sulfur compounds are present in a variety of colorfulfoods including broccoli, garlic and pineapple. Sulfur-containing compounds in plantsare active, or at least protective, against cancer because many pathogens are deterredby sulfur. Sulfur compounds also chelate mercury out of the body. The crucifer family--which includes broccoli, Brussels sprouts, cabbage, cauliflower, mustard greens,radishes and turnips--has many sulfur-containing compounds as well as indoles, asubclass of phytonutrients that binds chemical carcinogens and activates detoxificationenzymes, mostly in the gastrointestinal tract. Indoles and related compounds may

promote metabolism of carcinogens as well as improve estrogen balance, which couldreduce the risk of estrogen-related cancers such as breast cancer. The lily familyincludes garlic (Allium sativum) and onions (Allium cepa), both of which also containsulfur compounds. Studies have shown the sulfur compounds diallyl disulphide anddiallyl trisulfide--two of the active agents in garlic oil--and S-allyl cysteine--found incrushed garlic--to inhibit tumor metabolism and enhance immune response.



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Allyl sulfides also enhance glutathione S-transferase enzyme systems, which arebiochemical pathways involved in the liver's detoxification of carcinogenic substances.Allium species also have immune-enhancing actions that include promotion of

lymphocyte synthesis, cytokine release, phagocytosis and natural killer-cell activity.Several animal studies have shown that garlic and onions prevent cancer and inhibit theprogression of existing cancers, especially stomach and gastrointestinal cancers. Garlicappears particularly effective in reducing the risk of N-nitroso-induced cancers. N-nitroso compounds, also known as nitrosamines, are potent carcinogens formed withinthe intestines as a result of bacterial degradation of nitrates and nitrites, two commonfood chemicals used in the processing of ham, sausages and other meat products.All forms of garlic have been shown to have some medicinal activity. Pineapples containbromelain, a sulfur-rich proteolytic enzyme that has been investigated for antitumoreffects. U.S. and French research shows oral bromelain can reduce cancer in animals.Some documented cases show cancerous tumors regressing as a result of bromelain

therapy. Bromelain may also have antimetastatic effects. It has been examined in vitroto both oppose leukemia by promoting the normalization of blood cells and to reducemetastasis in lung-cancer cells.Other protective phytochemicals include the caffeic, ferulic and ellagic acids, which havebeen shown to degrade carcinogenic substances. Among other things, caffeic acid helpsdegrade carcinogens, and ferulic acid helps prevent nitratesin the digestive tract frombeing converted into the carcinogenic nitrosamines. Caffeic and ferulic acids are foundin green tea. Ellagic acid, which is particularly plentiful in pomegranates, also preventscarcinogen oxidation of cellular membranes. Ellagic acid is also found in blueberries,grapes, raspberries and strawberries.

Limonene is a bioflavonoid substance found in citrus rinds that stimulates both theglutathione transferase and the cytochrome p-450 liver detoxification systems. Theseenzymatic liver reactions break down carcinogenic substances in the body and helpprevent them from damaging cellular DNA. Another bioflavonoid, quercitin, isubiquitous in higher plants and has been widely studied for its antioxidant andconcomitant anticancer actions.

REVIEW OF LITERATURE

Carotenoids are a subclass of terpenes that are present in citrus fruits, cruciferousvegetables, spinach, tomato, yam, egg plant, mint, basil, and cherries. Terpenes areplant foods that act as antioxidants. Alpha carotene inhibits tumor growth. Lycopene is acarotenoid found in dark yellow orange and deep green vegetables and fruits, especiallytomatoes. It is the most effective biological singlet-oxygen quencher, two times aspowerful as beta-carotene in the destruction of free radicals. Research has shown thatlycopene-rich foods reduce the risk of prostate cancer. Carotenoids like lutein andzeaxanthin reduce the risk of lung and breast cancer.



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Limonoids are found in citrus fruits like grape fruit and orange juice and act as chemopreventive agents that induce enzymes in the liver's phase I and II enzyme detoxificationsystem. This system detoxifies carcinogens by making them more water soluble for

excretion. Grape juice and red wine are good sources of phenols and phenoliccompounds. Flavonoids scavenge free radicals and their complexes. By scavengingactivated mutagens and carcinogens, flavonoids may also decrease the risk of cancer.Caffeic and ferulic acids present in whole grains have been classified as cancerinhibitors. They act by preventing the formation of carcinogens from precursorcompounds and by blocking the reaction of carcinogens with critical cellmacromolecules. The potentially anticarcinogenic properties of these phenoliccompounds involve the induction of detoxification systems in the cell. Isoflavones arefound in beans and legumes, especially soy and its products. The phytochemical in soyfoods acts as an antioxidant and carcinogen blocker or tumor suppressor and may exerta protective effect against hormone-related cancers like breast and prostate cancer.

Thiols are sulphur containing phytonutrients found in cruciferous vegetables. Theseorganosulphuric compounds regulate the enzymes involved in the detoxification ofcarcinogens and other foreign compounds. Organo sulphur compounds are also found inthe allium or onion family including garlic, shallots, and leeks. Lignans arephytochemicals found in flax seeds, wheat bran, and barley, and they have a protectiveeffect against hormone-sensitive cancers by virtue of their interference with themetabolism of sex hormones. Phytic acid forms chelates with various metals thatsuppress iron-catalyzing redox reactions that can be pretty damaging to tissues. Colonicbacteria produce oxygen radicals in appreciable amounts, and dietary phytic acid cansuppress damage to the intestinal epithelium and neighboring cells. To date, several

hundred scientific studies focused on the activity of non-nutritional compounds presentin the diet, preventing the occurrence of degenerative diseases, such as cancer. Thisheterogeneous class of molecules, generally known as phytochemicals includes vitamins(carotenoids) and food polyphenols, such as flavonoids, phytoalexins, phenolic acidsindoles and sulfur rich compounds (Russo 2007; Sporn and Suh 2002 and Surh, 2003).More than 10,000 phytochemicals have been described, and among them more than6,000 compounds are included in the class of flavonoids (Hairborne 1993). They arewidely present in plant derived foods and beverages (fruits, vegetables and beveragesuch as tea, wine beer and chocolate), and in many dietary supplements or herbalremedies. Due to the variety of their physiological roles in plant tissues in regulatingenzymes involved in cell metabolism and in mechanisms of defence against foreignagents (radiations, viruses, parasites), phytochemicals have been associated topleiotropic effects in animal cells. Phytochemicals attracted scientists interests sincethe demonstration that their biological targets in mammalian cells were the sameinvolved in inflammatory processes and oncogenic transformation, such alterations ofcell cycle control, apoptosis evasion, angiogenesis and metastases.



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In addition, a large number of epidemiological studies suggest that a daily intake ofphytochemicals can reduce the incidence of several types of cancers (Russo 2007; Spornand Suh 2002; Russo et al. 2005 and D'Incalci et al. 2005). However, we and others

already underlined the discrepancy between phytochemical concentrations applied ininvitro studies. In fact, many phytochemicals, including polyphenols, are rapidly degradedand metabolized in the human body. Moreover, genetic variation in pathways affectingabsorption, metabolism, and distribution of these natural substances, could influenceexposure at the tissue level, thus modifying disease risk in individuals (Manach et al.2009 and Ross, 2007). Nevertheless, this wide group of natural molecules represents apromising class as anticancer drugs, since their multiple targets in cancer cells, withlimited toxic effect on normal cells. Phytochemicals can prove their therapeutic efficacyin mono-treatments or in association with classical chemotherapeutic drugs. In thelatter case, a double positive effect can be expected: i. phytochemicals can synergizewith cytotoxic drugs, increasing their efficacy and lowering the toxic side effects on

normal cells; ii. Combined treatment can delay resistance onset.Despite this encouraging preamble and the abundant literature describing the molecularmechanisms triggered by phytochemicals to inhibit cell growth and induce apoptosis incancer cells, only few of them entered clinical trials. Here, we will focus our attention ona selection of representative molecules, namely isothiocyanate, curcumin, genistein,epigallocatechin gallate, lycopene and resveratrol, largely present in the literature. Foreach of them, we will summarize their putative mechanism(s) of action from in vitro andanimal studies, and the current status of their clinical application in view of theirrealistic adoption as single chemotherapeutic agents or as chemo-sensitizers, inassociation with canonical and novel anti-cancer drugs.

Cranberry fruit has a diverse phytochemical profile that includes 3 classes of flavonoids(flavonols, anthocyanins, and proanthocyanidins), catechins, hydroxycinnamic and otherphenolic acids, and triterpenoids. Several groups of researchers examined activity ofwhole polyphenolic extracts of the fruit or spray-dried juice. Our group developed abioassay-guided fractionation approach to identification of antitumorigenic compoundswhile researching plants used in traditional Peruvian medicine (Neto et al. 2000). Ourstrategy used a simple NCI tumor growth inhibition assay (Skehan et al. 1990) to screenfor activity in several tumor cell lines. Antitumor activities of not only whole cranberryfruit and juice extracts has been examined but also individual compounds and groups ofcompounds to identify active constituents. Curcumin is a natural phytochemicalobtained from dried root and rhizome of Turmeric (Curcuma Longa). It has been shownto interfere with multiple cell signaling pathways, including apoptosis (activation ofcaspases and downregulation of antiapoptotic gene products), proliferation (HER-2,EGFR, and AP-1), angiogenesis (VEGF), and inflammation (NF-kappaB, TNF, IL-6, IL-1,COX-2, and 5-LOX). In the last decade it has been much explored and various syntheticanalogues have been prepared and evaluated for various pharmacological activities.



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Most of the analogues have shown very good anticancer activity in various models andvarious cell lines. However, some analogues have also shown antioxidant, anti-HIV,antimutagenic, antiangiogenic, antimalarial, antitubercular, antiandrogenic, COX

inhibitory activities (Agrawal and Mishra 2010).Ficus racemosaextract at a dose of 200 and 400 mg/ kg when given orally a significantdecrease in lipid peroxidation, xanthine oxidase, glutamyl transpeptidase andhydrogen peroxide (H2O2) generation with reduction in renal glutathione content andantioxidant enzymes generated by potassium bromate (KBrO3), a nephrotoxic agent thatinduces renal carcinoma in rats. There was significant recovery of renal glutathionecontent and antioxidant enzymes (Veerapur et al 2009). This suggests that Ficusracemosaextract is a potent chemopreventive agent and suppresses (KBrO3) mediatednephrotoxicity in rats. Fruit extracts of Ficus religiosaexhibited antitumor activity in thepotato disc bioassay. None of the tested extracts showed any marked inhibition on theuptake of calcium into rat pituitary cells GH4 C1 (Mousa 1994).

Combretastatins were isolated from the bark of the South African tree Combretumcaffrum (Combretaceae). Combretastatin is active against colon, lung and leukemiacancers and it is expected that this molecule is the most cytotoxic phytomoleculeisolated so far (Itokawa and Wang 2005). Emodin (1, 3, 8-trihydroxymethylanthraquinone) is a naturally occurring anthraquinone present in the roots andbarks of Cassia tora as an active ingredient. At present, its role in combinationchemotherapy with standard drugs to reduce toxicity and to enhance efficacy is pursuedvigorously. Its additional inhibitory effects on angiogenic and metastasis regulatoryprocesses make emodin a sensible candidate as a specific blocker of tumour associatedevents. Additionally, because of its quinone structure, emodin may interfere with

electron transport process and in altering cellular redox status, which may account forits cytotoxic properties in different systems. This biological property of emodin moleculeis offering a broad therapeutic window, which in future may become a member ofanticancer (Wu et al. 2001).Polyphenols particularly are among the diverse phytochemicals that have the potentialin the inhibition of carcinogenesis (Liu 2004). Phenolics acids usually significantlyminimize the formation of the specific cancer- promoting nitrosamines from the dietarynitrites and nitrates. Glucosinolates from various vegetable sources as broccoli,cabbage, cauliflower, and Brussel sprouts exert a substantial protective support againstthe colon cancer. Regular consumption of Brussel sprouts by human subjects (up to 300g.day1) miraculously causes a very fast (say within a span of 3 weeks) an appreciableenhancement in the glutathione-S- transferase, and a subsequent noticeable reductionin the urinary concentration of a specific purine meltabolite that serves as a marker ofDNA-degradation in cancer. Isothiocyanates and the indole-3- carbinols do interferecategorically in the metabolism of carcinogens thus causing inhibition ofprocarcinogen activation, and thereby inducing the phase-II enzymes, namely:



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NAD(P)H quinone reductase or glutathione S-transferase, that specifically detoxify theselected electrophilic metabolites which are capable of changing the structure of nucleicacids. Sulforaphane (rich in broccoli) has been proved to be an extremely potent phase-

2 enzyme inducer. It predominantly causes specific cell-cycle arrest and also theapoptosis of the neoplasm (cancer) cells. Sulforaphane categorically produces d-D-gluconolactone which has been established to be a significant inhibitor of breast cancer.Indole-3-carbinol (most vital and important indole present in broccoli) specificallyinhibits the Human Papilloma Virus (HPV) that may cause uterine cancer. It blocks theestrogen receptors specifically present in the breast cancer cells as well as downregulates CDK6, and up regulates p21 and p27 in prostate cancer cells. It affords G1 cell-cycle arrest and apoptosis of breast and prostate cancer cells significantly and enhancesthe p 53 expression in cells treated with benzopyrene. It also depresses Akt, NF-kappaB,MAPK, and Bel-2 signaling pathways to a reasonably good extent. Phytosterols block thedevelopment of tumors (neoplasms) in colon, breast, and prostate glands. Although the

precise and exact mechanisms whereby the said blockade actually takes place are notyet well understood, yet they seem to change drastically the ensuing cell-membranetransfer in the phenomenon of neoplasm growth and thereby reduce the inflammationsignificantly. A grass obtained from the plant Cymbopogoncitratus belongs to the familycitronella, lemon grass as an herb has been used for centuries for its positive healtheffects. The fresh grass is used in Indigenous medicine systems around the world.Recently the essential oil has been the subject of scientific studies regarding its effectson cancer cells. Lemon grass appears to be effective as forms of Chemotherapy causingcell death to occur. The research indicates that the oil has a promising anticanceractivity and causes loss in tumor cell viability by activating the apoptotic process. The

studies indicate that lemon grass essential oil with its low toxicity has the potential ofbeing an inexpensive, alternative treatment in the future (Koganov et al. 1994 andSieges et al. 1999). Wheat Grass is known as wholesome food and the king of alkaloidfoods as it is high in alkalinity that helps to fight off acidic body. It contains chlorophyllwhich is having similar structure of hemoglobin, known as Green blood. It increasesproduction of hemoglobin that Kills cancer by getting more oxygen. Selenium,superoxide dismutase (SOD) and abscisic acid are other anticancer agents present inthis. Since an acidic body is a magnet of chronic diseases, taking wheat grass helps toprevent cancer by balancing the pH and bring it to the desired alkalinity level in ourbody (Sheela et al. 2010). Sea-Buckthorn acts by enhancing immune system whichcontains very high amounts of antioxidant called carotenoids. Sea-buckthorn preventsthe growth of cancer cells and also preventing free radical oxidation. Seeds are in rich ofunsaturated fatty acids which is good for vascular system. Fruits pulp has high vitamin Eresponsible for the potent anticancer properties. Lingzhi used in Japan, it is a fungusknown as Herb of deathlessness, Herb of longevity and Celestial herb. It has beenpraised for its promoted vitality and longevity.



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Lingzhi (Gandoerma lucidum) is a mushroom i.e. rich in beta-D-glucose (using water alkali extract) that have a antitumor activities which currently used as an adjunctive intreatment of reducing side effects of chemotherapeutic agents. Amalkai is an Ayurvedic

plant, known as a mother of Healing system. It contains vitamin C and superoxidedismutase (SOD) and other antioxidants that fight off damaging free radicals to preventcancer. It is also rich in polyphenols, tannin, Bioflavonoids and amino acids(Krishnaswami and Raghuramuls 1998). Garlic has anticancer compound called duallysulfide. Raw -uncooked garlic i.e. chopped has much more potent anticancer effect thangarlic supplements (kken et al. 1999). Zingiber officinale belonging to familyZingiberaceae contains pungent ingredients in which gingerol and pardol have shownantitumor promotional and Anti-proliferative effects. Aloe vera and other species ofaloe contain aloe emodin which activates the macrophages to fight cancer. Aloe veraalso contains acemannan which enhances the activity of immune cells against cancer.Crude extract of Viburnum foetens showed remarkable anticancerous activity against

MCF-7 cell line at all concentrations in a dose dependent manner. The averageabsorbance decreased by increasing the concentration of crude extract. Highestabsorbance of 0.2006 was recorded when determining 28.4% inhibition at 10 g/ml,while at the concentration of 500g/ml of crude extract, 0.065 absorbance wasrecorded with 98.5% inhibition (Yamin et al. 2010). Anti-tumour activity of Cassia fistulaseed extract based on cytological studies reveal that a reduction in the mitotic activitycan be the leading mechanism of action against tumorigenesis. Indeed the appearanceof membrane blebbing and intracytoplasmic vacuoles in the treated tumour cellssuggest that these pathways may account for the reduction in tumour volume (Gupta etal. 2000). Fractions (EtOAc and n-BuOH) of different parts of Conocarpus erectus L. were

investigated in vitro towards two kinds of human cancer cell lines; liver carcinoma cellline (HepG2) and breast carcinoma cell line (MCF-7) at the National Cancer Institute inEgypt (El-Sayed et al. 2012). The methanol and fractionated extracts (hexane, ethylacetate and water) of Alpinia mutica (Zingiberaceae) rhizomes were investigated fortheir cytotoxic effect against six human carcinoma cell lines, namely KB, MCF7, A549,Caski, HCT116, HT29 and non-human fibroblast cell line (MRC 5) using an in vitrocytotoxicity assay. The ethyl acetate extract possessed high inhibitory effect against KB,MCF7 and Caski cells (IC50 values of 9.4, 19.7 and 19.8 g/mL, respectively). Flavokawin B(1), 5, 6-dehydrokawain (2), pinostrobin chalcone (3) and alpinetin (4), isolated from theactive ethyl acetate extract were also evaluated for their cytotoxic activity. Of these,pinostrobin chalcone (3) and alpinetin (4) were isolated from this plant for the first time.Pinostrobin chalcone (3) displayed very remarkable cytotoxic activity against the testedhuman cancer cells, such as KB, MCF7 and Caski cells (IC50 values of 6.2, 7.3 and 7.7g/mL, respectively). This is the first report of the cytotoxic activity of Alpinia mutica(Abdul et al. 2011).



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The stem of V. diospyroides Symington, an endemic medicinal and fragrant dipterocarpof Thailand peninsula, has strong anticancer activity (Seo et al. 1999 and Kinghorn et al.2011). Apple contains anti cancer substances known as phenols, which neutralize

certain carcinogens, disrupt the transformation of precancerous cells into the cancerousones, and stimulate the bodys production of natural cancer fighters. Pectin, a naturalfiber present in apple, is known to reduce the risk of colon cancer. Apple is a good heartmedicine, lowers the blood cholesterol, lowers blood pressure, stabilizes blood sugar,regulates appetite, kill infectious viruses. Apricot is a cancer inhibitor, especially lung,smoking related cancer.Asparagus is commonly referred to as the king of vegetablesby the ancient Romans and Greeks, can be used to treat arthritis, tooth ache andinfertility. Researchers have found out that it contain the potent antioxidantglutathione, which is helpful in the fight against cancer, cataracts and heart diseases.Barley lowers blood cholesterol, inhibits cancer and improves bowel functions, relievesconstipation. Beans power houses of nutrition are also versatile in kitchen. They contain

good amounts of protease inhibitors like lignans, phytoestrogens and fiber. All arepotent cancer fighters. Studies show that people who make beans a significant part oftheir diet are less likely to have breast cancer and pancreatic cancer. Isoflavones andflavonoids compounds that are commonly found in various legumes including soybeansare very effective antitumour compounds. One of the most important components inbeans is Genistein as it closely resembles human estrogen. For this reason it is veryimportant to include beans, especially soybeans as part of an anticancer diet.Fermented soybeans products such as miso, tempeh and shoyu tamari go throughcomplex chemical processes that are of particular benefit in the prevention andtreatment of cancer. Research has shown that soybean products contain five cancer

preventive or reversal chemical agents namely (1) protease inhibitors, which hold offactivation of the specific oncogenes that cause cancer; (2) phytate, which binds iron inthe intestines to prevent it from generating free radicals resulting in cancer; (3)phytosterols, which neutralize the breakdown of cholesterol and reduce thedevelopment of colon tumors and skin cancer; (4) saponins, which stop cellularmutations that could inevitably lead to cancer; (5) isoflavones, which are plantestrogens with strong inhibiting effects in hormone related malignancies such asprostrate, ovarian, cervical and breast cancers. The frequent consumption of cruciferousvegetables like Broccoli is associated with a decreased risk for cancer. Women musthave concern about breast cancer, while men should be more worried about prostatecancer. If one is concerned about either breast cancer or prostate cancer, he or sheshould realize that eating cruciferous vegetables, such as broccoli and cabbage, is reallygood for him/her. Eating half of a head of cabbage each day or extremely large amountsof other cruciferous vegetables is what it would take to get the kind of health riskreduction one is looking for and that is neither practical nor palatable (Mohammad et al2009).



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Anona muricata extract had greater anticancer potential; Anona muricata was activeagainst the lung cancel lines at IC50 value of 7.29 while that of A.paniculatawas 10.60.This shows that the extract ofA. muricataandA. paniculatawere active against the lung

cancer cell line. AM and AP contained copious amount of phytoestrogens such asflavonoids which could be responsible for the anticancer activity. Some groups offlavonoids are known for their anti-inflammatory and anti-allergic, anti-thrombotic,vasoprotective and antitumour activities (Anne et al 2007). Anticancer evaluation ofAdiantum venustum Don.Against Ascites carcinoma in animal model indicated that theethanolic extract possess significant anti-cancer activity also reduce elevated level oflipid Peroxidation due to higher content of terpenoids and flavanoids .the ethanolicextract of Adiantum venustum could have vast therpantic application against cancer(Pandey and Devmrari 2009). Anti-tumor activity of different concentrations of ethanolicextracts of Kaempferia galanga, Clerodendrum viscosum, Jatropha curcus and Lensculinariswas evaluated. Ethanolic extracts demonstrated strong inhibitory effect on the

growth of cancer cells in DLA tumor bearing mice. Based on in vitro studies like brineshrimp lethality assay, potato disc method and onion root tip inhibition studies, theethanolic extract of Kaempferia galanga was found to possess significantly betteranticancer activity (Bagya et al 2011).Asclepias curassavica (L.)contains highly potentialesterified polyhydroxy pregnane glycoside that shows antitumour and anticancerproperty (Kinghorn 2001). Extracts (methanol) of the leaves, stem and rhizome ofBoesenbergiaspecies possess total phenolics and flavonoid contents, antioxidant as wellas anticancer properties. The plants revealed the presence of polyphenols such asquercetin, kaempferol, rutin, naringin, hesperidin, caffeic acid, p- coumaric acid, ferulicacid, sinapic acid, chlorogenic acid, gallic acid, luteolin and diosmin by using High

Performance Liquid Chromatographic (HPLC). Cytotoxicity assay of B. rotunda showedthe most prominent and promising result as anticancer medicinal plant. It showedpositive antiproliferative effect against five cancer cell lines: ovarian (CaOV3), breast(MDA-MB-231 and MCF-7), cervical (HeLa) and colon (HT-29) cancer cell lines with 3-(4,5-dimethylthiazol-2-yl) -2, 5- diphenyltetrazolium bromide (MTT) assay conducted. Inaddition, the rhizome of B. pulchella var attenuate and B. armeniaca shown positiveresult in cytotoxicity assay tested against breast cancer (MCF-7). Thus, the Boesenbergiaspecies investigated would be a promising anticancer remedy for breast cancer (Ling etal 2010). Garcinol, a polyisoprenylated benzophenone, is extracted from the rind of thefruit of Garcinia indica. Its biological activities, specifically its anticancer potential is aresult of recent scientific investigations. The anticarcinogenic properties of garcinolappear to be moderated via its antioxidative, anti-inflammatory, antiangiogenic, andproapoptotic activities. In addition, garcinol displays effective epigenetic influence byinhibiting histone acetyltransferases (HAT 300) and by possible posttranscriptionalmodulation by mi RNA profiles involved in carcinogenesis.



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In vitro as well as some in vivo studies have shown the potential of this compoundagainst several cancers types including breast, colon, pancreatic, and leukemia.Although this is a promising molecule in terms of its anticancer properties,

investigations in relevant animal models, and subsequent human trials are warranted inorder to fully appreciate and confirm its chemo preventative and/or therapeuticpotential (Saadat and Gupta 2012).lycopene,the carotenoid in tomatoes that accounts for their red color. Consumption ofwhole, cooked tomatoes protect against prostate cancer and provide anticancer activity.In a study conducted in 2005, cancer patients ate tomato sauce on pasta for just threeweeks before their PSA levels were retested and compared to baseline. Patientsexperienced a significant reduction in blood levels of PSA, indicating that the cancerprogression was slowed or stopped. The researchers also reported that cancer cellswere dying at a rapid rate. They believe that other phytochemicals in the tomatoes maybe acting synergistically with the lycopene to produce these effects (Stacewicz-

Sapuntzakis and Bowen 2005). Methanol extract of Heritiera fomesBuch. Ham. leaf andstem powder showed anticancer properties with 40 % inhibition against B16 mousemelanoma (in vitro system) and Ehrlich Ascites Carcinoma (EAC) in Swiss albino mice (invivo system). The partial characterizations of the methanol extract by TLC, HPLC, 1HNMR and FTIR spectral analysis revealed phenolic as the lead compounds. Overallresults showed that both the leaf and stem extracts of H. fomes possess stronganticancer properties along with the presence of most of the phytochemicals (Patra andThatoi 2013). Grape Seed Extract have excellent anticancer and chemopreventiveefficacy against skin, colorectal, prostate, and breast cancers. Apart from this anticancerefficacy of this extract has also been observed against human lung cancer A427, A549,

and H1299 cells, human gastric adenocarcinoma CRL-1739 cells, oral squamous cellcarcinoma CAL27 and SCC25 cells, Jurkat, U937, and HL-60 (Ye etal 1999; Akhtar et al2009 and Gao et al 2009). GSE as well as red wine have been shown to significantlyreduce the number of metastatic nodules on the surface of lung in Swiss miceinoculated with B16F10 melanoma cells (Martnez et al 2005). Scutellaria baicalensisis awidely used Chinese herbal medicine historically used as anti-inflammatory andanticancer therapy that is being tested as a treatment for prostate cancer. Two humanprostate cancer cell lines (LNCaP, androgen dependent, and PC-3, androgenindependent) were assessed for growth inhibition when exposed to S. baicalensis. S.baicalensisexerted dose- and time-dependent increased growth inhibition in both celllines. After treatment with S. baicalensis, PGE2 synthesis in both cells was significantlyreduced, resulting from direct inhibition of COX-2 activity rather than COX-2 proteinsuppression. S. baicalensisalso inhibited prostate-specific antigen production in LNCaPcells. Finally, S. baicalensissuppressed expression of cyclin D1 in LNCaP cells, resulting ina G1 phase arrest, while inhibiting cdk1 expression and kinase activity in PC-3 cells,



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ultimately leading to a G2/M cell cycle arrest. In animal studies, after a 7-weektreatment period with S. baicalensis, tumor volume was reduced by 50%, demonstratingthat

S. baicalensismay be a novel anticancer agent for treating prostate cancer (Ye et al

2007). Methanol extract of Scutellaria orientalis showed potent anti-leukemic activityagainst HL-60 cell line (Ozmen et al 2010). The water extract of Rheum officinaleexhibited significant antiproliferative activity by inducing apoptosis in MCF-7 and A549cell lines (Li etal 2009). A potent antiproliferative activity was also reported for thehexane extract of Casearia sylvestris stem bark against different cancer cell lines(Mesquita et al 2009) and the butanol extract of Pfuffia paniculatademonstrated highcytotoxic activity against MCF-7 cell line (Nagamine et al 2009). The aqueous methanolextract of Ononis hirtaand Inula visocsa showed high ability to selectively target MCF-7cancer cells and induced apoptosis (Talib and Mahasneh 2010a). Genistein, daidzein andisoflavonoids in soybean are thought to play an important role in breast cancer

prevention (Singh et al 2002 and Wang et al 2002). Two other examples of naturalcompounds with anticancer properties are quercetin and apigenin. Quercetin is one ofthe major flavonoids found in the human diet which exerts a dose-dependent inhibitoryeffect on cell proliferation with cell cycle arrest in G2/M phase. Quercetin has also beenshown to inhibit cell proliferation in colon carcinoma (HCT-116 and HT-29) andmammary adenocarcinoma (MCF-7) cell lines after 24 h of exposure (Ramos 2007 andOng et al 2007). Apigenin a flavone found in celery has antiproliferative effect with cellcycle arrest in G2/M in MCF-7 cells and induces caspase activities in HL-60 cells (Yin et al2001 and Wang et al 1999). Bioassay results of the total methanolic extract of Kigeliapinnatastem bark showed that the total extract displayed prominent cytotoxic activity

in a concentration-dependent manner. The cell lines with most pronounced chemosensitivity to the extract were the breast cancer derived MCF-7, the murine Lewis lungcancer (cell line) and the acute T-cell leukemia SKW-3, whereby the IC50values weresignificantly lower as compared to those obtained in the other cell lines (Denitsa et al2012). Ethanol Extract of Impatiens balsamina was investigated for anticancer and in-vitro cytotoxic activities against transplantable tumors and human cell line. In vitrocycotoxicity was evaluated in Hela and NIH3T3 cells by MTT assay and in-vivo antitumoractivity with Daltons ascites lymphoma (DLA) tumor bearing mice. The extract exhibitedstrong in vitro cytotoxicity against Hela cell line, it was found to be safe with normal cell.EEIB at the doses 200 and 400 mg/kg significantly increase the life span and decrease inthe cancer cell number and body weight (P


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EEIB at the doses 200 and 400 mg/kg significantly increase the life span and decrease inthe cancer cell number and body weight (P


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Anti-tumor potential of the crude extract and isolated compounds from inflorescencesof Piper claussenianumrevealed the presence of phenolic metabolites in the methanolcrude extract. Phytochemical procedures lead to the isolation of the major flavonoids,

2,6-dihydroxy-4-methoxychalcone, 5,7-dihydroxyflavanone and 5-methoxy-7-hydroxyflavanone that were assayed for inhibition or viability stimulation of the humanbreast cancer cell line MCF-7. The results suggest the 2,6-dihydroxy-4-methoxychalcone as the biologically active compound in the crude methanol extract ofinflorescences from P. claussenianum. The crude extract was found as potential naturalsource of compounds with breast cancer cell inhibition properties (Marques et al 2013).Allium sativum contains more than 100 biologically useful secondary metabolites, whichinclude alliin, alliinase, allicin, Sallyl- cysteine (SAC), diallyldisulphide (DADS),diallyltrisulphide (DATS) and methylallyltrisuphide (Charfenberg et al 1990).Aloe veracontains aloe-emodin, which activates the macrophages to fight cancer.Aloe vera alsocontains acemannan, which enhances activity of the immune cells against cancer.Aloevera is found to inhibit metastases (Pecere et al 2000). Aesculus indica (Linn.)(Sapindaceae) is an ethanobotanically important plant species traditionally usedagainstrheumatism, skin and vein complaints. Cytotoxic potential of Aesculus indicacrude leaf extract and its fractions was investigated against MCF-7 cell line. Crudeextract of Aesculus indica was prepared in methanol by maceration technique. Crudeextract was fractionated into four organic and one aqueous fraction on polarity basis.MTT assay was used to evaluate the reduction of viability of MCF-7 breast cancer cellline. Cell viability was inhibited by Aesculus indica crude extract in a dose dependentmanner ranging from 34.2% at 10 g/ml to 94% at 500g/ml. Activity was found in anascending order from hexane showing 29.8% inhibition to aqueous fraction indicating

maximum inhibition, 60%. Phytochemical analysis of crude and fractionated extractsrevealed presence of flavonoids, saponins, coumarins and tannins upto varying degrees.Methanol and aqueous fraction of methanol extract of Aesculus indica can be goodsource of cytotoxic compounds (Bibi et al 2012).Morinda citrifolia showed of cancer preventive effective on both clinical practice andlaboratory animal models (Wang et al 2001). An alcoholic extract of Biorhythmssensitivum for antitumor activity could inhibit the solid tumor development on miceinduced with Daltons lymphoma ascites (DLA) cells and increase the life span of micebearing Ehrlich ascites carcinoma (EAC) tumors (Guruvayoorappan and Kuttan 2007).Edible fruits and berries served the source for novel anticancer agents, given thatextracts of those foods have demonstrated cytotoxic activity against tumor cell lines(Ferguson et al 2006). Nimbolide, a triterpenoid extract from the flowers of the neemtree was found to have antiproliferative activity against some cancer cell lines (Roy et al2007). Semecarpus anacardium Linn. nut milk extract exerts its anticancer effectthrough quenching-reactiveoxygen species (Arulkumaran et al 2006). The Pomegranateextracts inhibits the growth of breast cancer cells (Jeune et al 2005).



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Brassinosteroids, steroid plant hormones are promising leads for potential anticancerdrugs (Malikovia et al 2007). The Careya arborea bark significantly reduced the solidtumor volume induced by DLA cells (Natesan et al 2007). The methanol extract of

Bauhinia racemosastem bark exhibited antitumor effect in EAC bearing mice (Gupta etal 2004). The antitumor activity of the ethanol extract of Indigofera aspalathoideswasestablished (Rajkapoor et al 2004).

CONCLUSIONFrom the present review, it can be concluded that cancer is the leading cause of deathin developing countries like India. As there is an enormous increase in the populationday by day, the alternative therapy in the market is getting its glimpse. The cheap herbaldrug treatment may highly be recommended to the rural and poor people to treateffectively the cancers of various type is an ideal choice. Based on that the siddhamedicines are coming up in combination with metals and other essential supplementsto improve the immune status of the cancer patients in India. The above survey revealsthe role of Indian medicinal plants and the various phytochemicals may be treatedeffectively for cancer. The available literature finds to be very impressive which may givean indication for the therapeutic usefulness. The isolation, identification of activeprinciples and pharmacological studies of the active phytoconstituents may beconsidered and studied elaborately to treat effectively for various types of cancer.

ACKNOWLEDGEMENTSI thank Dr. Rajni Singh, Additional Director & Acting Head, Amity Institute of MicrobialBiotechnology and Ms. Smitha M.S., Assistant Professor, Amity Institute of MicrobialBiotechnology for their constant support and encouragement.

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Corresponding author: Dr. Arti Goel,Amity Institute of Microbial Biotechnology, AmityUniversity, Sector- 125, Noida (U.P.) 201301, IndiaEmail Id:[email protected]


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